Facilitating Translational Nanomedicine via Predictive Safety Assessment

Abstract

Extensive research on engineered nanomaterials (ENMs) has led to the development of numerous nano-based formulations for theranostic purposes. Although some nano-based drug delivery systems already exist on the market, growing numbers of newly designed ENMs exhibit improved physicochemical properties and are being assessed in preclinical stages. While these ENMs are designed to improve the efficacy of current nanobased therapeutic or imaging systems, it is necessary to thoroughly determine their safety profiles for successful clinical applications. As such, our aim in this mini-review is to discuss the current knowledge on predictive safety and structure-activity relationship (SAR) analysis of major ENMs at the developing stage, as well as the necessity of additional long-term toxicological analysis that would help to facilitate their transition into clinical practices. We focus on how the interaction of these nanomaterials with cells would trigger signaling pathways as molecular initiating events that lead to adverse outcomes. These mechanistic understandings would help to design safer ENMs with improved therapeutic efficacy in clinical settings.During the past decades, engineered nanomaterials (ENMs) have been widely used in biomedical applications, such as nanomedicine, bioimaging, and tissue engineering, because of their unique biophysicochemical properties.1,2 With regard to nanomedicine applications, ENMs could be formulated as drug carriers that deliver the therapeutic reagents within the human body and increase their bioavailability and blood circulation half-life.2 Moreover, these nanocarriers could be functionalized to deliver the drug specifically to the desired target tissues (e.g., tumors) and release the payload sustainably over long periods, thereby eliminating the necessity of multiple drug administration and reducing its cytotoxic side effects toward healthy cells.2 In addition to their implementation in drug delivery, ENMs could be used for diagnostic and imaging purposes that would help to monitor the disease and administer the treatment more accurately. 2Past research in nanomedicine has led to the design of various nanomaterial-based therapeutic and diagnostic systems that are being investigated in experimental stages (e.g., in vitro and in vivo) and clinical trials or are commercially available to the corresponding patients (Table 1). Most commercialized nanomaterial-based therapeutic reagents use lipids, proteins, and polymers that could self-assemble and biodegrade with few side effects.3 Because of high biocompatibility of lipids, several commercial liposome-drug formulations have been developed, mostly relying on polyethylene glycol (PEG)-conjugated lipids, such as DOXIL, AmBisome, Epaxal, and Inflexal V, and are under clinical trials focusing on various types of disease treatments. 4,5 Polymer-based nanoparticles (NPs) also present low toxicity, but their surface functionalization may affect their safety. The most commonly used materials include PEG, ploy(lactic-co-glycolic) acid (PLGA...

Continued Efforts on Nanomaterial‐Environmental Health and Safety Is Critical to Maintain Sustainable Growth of Nanoindustry

“…Moreover, additional alternative test strategies and multiomics technology should be utilized more for nano-EHS assessment, which includes high throughput screening, predictive toxicology, genomics/epigenetics/metabolomics, and in silico approaches, to move nano-EHS from descriptive science to mechanism-based toxicology. [11,13,18,20,87] Especially, it is important to link the physicochemical properties of ENMs to the toxicological outcomes. [10][11][12]16,87,88] iii) After years of development, there are still enormous obstacles and limitations for the current computational models to precisely characterize nano toxicology.…”

“…[11,13,18,20,87] Especially, it is important to link the physicochemical properties of ENMs to the toxicological outcomes. [10][11][12]16,87,88] iii) After years of development, there are still enormous obstacles and limitations for the current computational models to precisely characterize nano toxicology. Thus, computational models (e.g., nano-oriented Quantitative Structure-Activity Relationship models, Nano-QSAR) should be improved to identify the key characteristics that dictate the nano-EHS.…”

Mechanistic Understanding of the Engineered Nanomaterial-Induced Toxicity on Kidney

“…In recent decades, engineered nanomaterials (ENMs) with novel physicochemical properties have been widely applied in various fields such as electronics, cosmetics, food additives, and biosensors [1,2], and global ENM production is estimated to be more than 300,000 tons per year [3][4][5]. However, their safety is drawing more and more attention [6]. With ENM exposure, they could be accumulated and reside in the environment that could further lead to significant health issues [7].…”

Evaluation of non-targeting, C- or N-pH (low) insertion peptide modified superparamagnetic iron oxide nanoclusters for selective MRI of liver tumors and their potential toxicity in cirrhosis

“…[9][10][11][12][13] Furthermore, SPIO has been widely used in diagnosis and therapy of other cancers such as prostate cancer diagnosis and drug delivery. [14][15][16][17][18][19] On the other hand, the potential cytotoxicity of SPIO has recently been considered as a major safety concern, [19][20][21] especially in chronic liver diseases due to SPIO induced iron overload resulting in increased risks of steatohepatitis and cirrhosis progression and liver lesions in obesity. [22][23][24][25][26] One way to enhance the safety prole of SPIO was to utilize the target-specic delivery strategy such as cRGD ligand or pH (low) insertion peptide (pHLIP).…”